Storage and release of catecholamines from adrenal medullary cells are affected by a variety of heavy metals, partially through interference with calcium-specific mechanisms involved in release of the neurotransmitter. The calcium-promoted fusion of isolated chromaffin granules (CG), and its inhibition by various heavy metals, are being studied as model processes for exocytotic release of catecholamines in vivo. The kinetics of calcium-promoted aggregation and fusion of the granules can be followed using fluorescence resonance energy transfer (FRET) techniques. The effect of calcium on granule membrane proteins labeled with fluorescent maleimides has directly demonstrated the fluid mosaic nature of the granule membrane. Calcium promotes FRET which is due to the aggregation of the membtanes. This component runs with a rate which is 5-10 times slower than aggregation itself. Fluorescently labeled lipid probes have been successfully inserted into chromaffin granule membranes. FRET studies of calcium promoted fusion of these membranes show that fusion also runs 5-10 fold slower than aggregation. These results imply that substantial rearrangement of the protein and lipid components of the membrane is required for fusion to occur. Heavy metal neurotoxicity may operate by interference with calcium-controlled cell processes. A soluble calcium-specific protein (synexin) isolated from chromaffin tissue or liver enhances the ability of calcium to aggregate chromaffin granule membranes. However, synexin has the same effect on a number of biological and artificial membranes which is related to their net negative surface charge. We have isolated a second protein (synexin II) from these sources with entirely different molecular weight, protease susceptibility and peptide fragments, suggesting that the aggregation phenomenon is best regarded as a convenient method for discovering calcium specific proteins. The chromaffin granule membrane contains several calmodulin binding proteins and the calcium-promoted fusion of artificial lipid vesicles with CG membranes may be under calmodulin control.